The long-term goal of this project is to understand the molecular mechanisms that program the events of yeast sporulation -- the process by which yeast forms gametes. This process begins with a diploid vegetative cell and yields an ascus containing four haploid meiotic products derived from that cell. Because the steps of yeast meiosis are like those of higher eukaryotes, it is expected that the mechanisms and machinery used in yeast may shed light on meiosis in higher organisms and thus provide insights into the molecular basis of infertility and birth defects in humans. Prior studies by others led to the hypothesis that the events of sporulation are determined by a transcriptional cascade involving sequential transcription of early, middle, and late genes. Prior studies by others also identified what appears to be a key decision-making point at pachytene, after replication and recombination but before the first meiotic division, which monitors completion of recombination. We have recently identified the regulatory protein, Ndt80p, that governs transcription of many of the middle sporulation genes and proposed that it may play a central role in the decision of cells to initiate meiotic divisions after completion of replication and recombination. In addition, we have carried out whole-genome expression studies using DNA microarrays which reveal that Ndt80p controls transcription of more than 150 genes during sporulation. The goal of this proposal is to determine how the program of sporulation is controlled using Ndt80p as a jumping off point. In particular, these studies seek to understand how Ndt80p synthesis and activity are regulated and how it functions to activate transcription of a large group of genes involved in chromosome segregation and spore morphogenesis. Learning about Ndt80 protein is likely to yield enormous insight on the decision to exit meiotic prophase and on the overall program of sporulation.